Exposure to residential green and blue space and the natural environment is associated with a lower incidence of psychiatric disorders in middle-aged and older adults: findings from the UK Biobank.

BACKGROUND: There is increasing evidence for the role of environmental factors and exposure to the natural environment on a wide range of health outcomes. Whether exposure to green space, blue space, and the natural environment (GBN) is associated with risk of psychiatric disorders in middle-aged and older adults has not been prospectively examined. METHODS: Longitudinal data from the UK biobank was used. At the study baseline (2006-2010), 363,047 participants (women: 53.4%; mean age 56.7 ± 8.1 years) who had not been previously diagnosed with any psychiatric disorder were included. Follow-up was achieved by collecting records from hospitals and death registers. Measurements of green and blue space modeled from land use data and natural environment from Land Cover Map were assigned to the residential address for each participant. Cox proportional hazard models with adjustment for potential confounders were used to explore the longitudinal associations between GBN and any psychiatric disorder and then by specific psychiatric disorders (dementia, substance abuse, psychotic disorder, depression, and anxiety) in middle-aged and older adults. RESULTS: During an average follow-up of 11.5 ± 2.8 years, 49,865 individuals were diagnosed with psychiatric disorders. Compared with the first tertile (lowest) of exposure, blue space at 300 m buffer [hazard ratio (HR): 0.973, 95% confidence interval (CI): 0.952-0.994] and natural environment at 300 m buffer (HR: 0.970, 95% CI: 0.948-0.992) and at 1000 m buffer (HR: 0.975, 95% CI: 0.952-0.999) in the third tertile (highest) were significantly associated with lower risk of incident psychiatric disorders, respectively. The risk of incident dementia was statistically decreased when exposed to the third tertile (highest) of green space and natural environment at 1000 m buffer. The third tertile (highest) of green space at 300 m and 1000 m buffer and natural environment at 300 m and 1000 m buffer was associated with a reduction of 30.0%, 31.8%, 21.7%, and 30.3% in the risk of developing a psychotic disorder, respectively. Subgroup analysis suggested that the elderly, men, and those living with some comorbid conditions may derive greater benefits associated with exposure to GBN. CONCLUSIONS: This study suggests that GBN has significant benefits for lowering the risk of psychiatric disorders in middle-aged and older adults. Future studies are warranted to validate these findings and to understand the potential mechanistic pathways underpinning these novel findings.

Combination of CRISPR/Cas9 System and CAR-T Cell Therapy: A New Era for Refractory and Relapsed Hematological Malignancies.

Chimeric antigen receptor T (CAR-T) cell therapy is the novel treatment strategy for hematological malignancies such as acute lymphoblastic leukemia (ALL), lymphoma and multiple myeloma. However, treatment-related toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have become significant hurdles to CAR-T treatment. Multiple strategies were established to alter the CAR structure on the genomic level to improve efficacy and reduce toxicities. Recently, the innovative gene-editing technology-clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease9 (Cas9) system, which particularly exhibits preponderance in knock-in and knockout at specific sites, is widely utilized to manufacture CAR-T products. The application of CRISPR/Cas9 to CAR-T cell therapy has shown promising clinical results with minimal toxicity. In this review, we summarized the past achievements of CRISPR/Cas9 in CAR-T therapy and focused on the potential CAR-T targets.

Detection and analysis of MEG signals in occipital region with double-channel OPM sensors.

BACKGROUND: Magnetoencephalography (MEG) has high temporal and spatial resolution and good spatial accuracy in determining the locations of source activity among most non-invasive imaging. The recently developed technology of optically-pumped magnetometer (OPM) has sensitivity comparable to that of the superconducting quantum interference device (SQUID) used in commercial MEG system. NEW METHOD: Double-channel OPM-MEG system detects human photic blocking of alpha rhythm at the occipital region of skull in the magnetically shielded environment via a wearable whole-cortex 3D-printed helmet. RESULTS: The alpha rhythm can be detected by the OPM-MEG system, the MEG signals are undoubtedly caused by photic blocking and similar with the results measured by SQUID magnetometer. COMPARISON WITH EXISTING METHODS: Due to the dependency of current commercial whole-cortex SQUID-MEG system on the liquid helium, the separation from the liquid helium space to the human head is usually at least a few centimeters. The wearable OPM-MEG system, however, can significantly improve the detection efficiency since its sensors can be mounted close to scalp, normally less than 1 cm. CONCLUSIONS: OPM-MEG system successfully detects alpha rhythm blocked by light stimulation and works well in the home-made magnetically shielded environment. OPM-MEG system shows a substitute for the traditional MEG system.

Crystal structure and catalytic activity of the PPM1K N94K mutant.

Protein Phosphatase Mg2+ /Mn2+ -Dependent 1K (PPM1K),also named as PP2Cm or branched-chain α-ketoacid dehydrogenase complex phosphatase, is a member of the metal-dependent phosphatase family and an important metabolic regulator. Single nucleotide polymorphisms (SNPs) in PPM1K contributing to protein functional defects have been found to be associated with numerous human diseases, such as cardiovascular disease, maple syrup urine disease, type 2 diabetes, and neurological disease. PPM1K N94K is an identified missense mutant produced by one of the SNPs in the human PPM1K coding sequence. However, the effects of the N94K mutant on its activity and structural property have not been defined. Here, we performed a detailed enzymological study using steady-state kinetics in the presence of pNPP or phospho-peptide substrates and crystallographic analyses of the wild-type and N94K PPM1K. The PPM1K-N94K significantly impaired its Mg2+ -dependent catalytic activity and structural analysis demonstrated that the N94K mutation induced a conformational change in the key residue in coordinating the Mg2+ in the active site. Specifically, three Mg2+ were located in the active site of the PPM1K N94K instead of two Mg2+ in the PPM1K wild type. Therefore, our results provide a structure basis for the metal ion-dependent PPM1K-N94K phosphatase activity.

Efficacy of prophylactic probiotics in combination with antibiotics versus antibiotics alone for colorectal surgery: A meta-analysis of randomized controlled trials.

This meta-analysis aimed to determine whether prophylactic probiotics in combination with antibiotics are superior to antibiotics alone in the prevention of surgical site infection (SSI) after colorectal surgery. Fourteen trials involving 1524 participants were included. Compared with antibiotics alone, prophylactic probiotics in combination with antibiotics reduced the risk of SSI as well as other complications, shortened the cumulative duration of antibiotic therapy. Current evidence suggested that probiotics in combination with antibiotics could be recommended.

Brachialis muscle transfer for reconstructing digital flexion after brachial plexus injury or forearm injury.

Restoration of digital flexion after brachial plexus injury or forearm injury has been a great challenge for hand surgeons. Nerve transfer and forearm donor muscle transfer surgeries are not always feasible. The present study aimed at evaluating the effectiveness of restoring digital flexion by brachialis muscle transfer. Ten lower brachial plexus- or forearm-injured patients were enrolled. After at least 12 months following surgery, the middle-finger-to-palm distance was less than 2.5 cm in six patients. In the other four patients with less satisfactory results, secondary tenolysis surgery was performed and the middle-finger-to-palm distances were reduced to 2.0-4.0 cm. The average grasp strength was 20 ± 4 kg. Elbow flexion was not adversely affected. In conclusion, brachialis muscle transfer is an effective method for reconstructing digital flexion, not only in lower brachial plexus injury, but also in forearm injury patients. LEVEL OF EVIDENCE: IV.

Effect of c-erbB2 overexpression on prognosis in osteosarcoma: evidence from eight studies.

C-erbB2 (HER-2/neu) plays an important role in the progression of several types of cancer by increasing tumor growth, migration, invasion, and metastasis and is associated with poor disease prognosis. Numerous studies examining the relationship between c-erbB2 expression and prognostic impact in patients with osteosarcoma have yielded inconclusive results. We therefore conducted a meta-analysis to provide a comprehensive evaluation of the prognostic role of c-erbB2 expression on 5-year survival, which compared the positive and negative expression of c-erbB2 in patients of the available studies. A detailed search was made in PubMed for relevant original articles published in English. Finally, a total of eight studies with 411 osteosarcoma patients were involved to estimate the relationship between c-erbB2 expression and 5-year overall survival. Positive expressions of c-erbB2 predicted poorer survival in osteosarcoma with the pooled RR of 1.53 (95 % CI 1.20-1.94, P = 0.0006). In conclusion, the findings from this present meta-analysis suggest that c-erbB2 overexpression is related to poor prognostic of osteosarcoma and can be a useful clinical prognostic factor for those patients.